1. Field of the Invention
The present invention describes a novel powder compartment for a single-use disposable pulmonary or nasal inhaler of simple construction, operation and low cost for the delivery of high dosages of pharmaceutical compounds.
Inhalers used for the delivery of pharmaceutical compounds have become widespread and include pressurized metered dose, nebulizers and powder-based inhalers. The latter category delivers the dose of medicinal powder using the energy generated by the patient's inspiratory effort and includes multi-use reservoir-based devices, re-usable devices supplied with unit-doses packaged in blisters, re-usable devices using unit-dose capsules loaded by the patient, and single-use disposable powder-based inhalers. The present invention is in this last category.
Powder-based inhalers have been used mainly for maintenance treatment of respiratory diseases such as asthma or the chronic obstructive pulmonary disease. However, single-use disposable devices have deserved considerable attention due to the need to treat situations were an infectious agent is being treated or is present in the mouth or airways and the elimination of the potential for inhaler contamination is thus required.
Furthermore, the effort to develop single-use disposable inhalers has also been fuelled by the growing interest in delivering to patients high payloads, in the range of 50 to 120 mg, of pharmaceutical compounds such as antibiotics, vaccines, proteins, peptides, insulin or other drugs systemically via the lung or nose through few, simple and intuitive interactions with the device. In such applications, pharmaceutical compounds that have been particle engineered by processing techniques such as spray drying or jet milling are normally characterized by high adhesion and cohesion properties resulting from low median particle size by volume, typically below 2 μm, in addition to low bulk density, typically in the range of 0.2 g/cm3-0.5 g/cm3.
Therefore, a major challenge is designing the mechanism for aerosolizing and dispersing large quantities, in the range of 50 to 120 mg, of highly cohesive and adhesive powders while minimizing the amount of powder retention in the device. In addition, a significant challenge is also the provision of deagglomeration mechanisms which ensure the break-up of such large quantities of highly agglomerated drug particles down to particles with an inhalable size of less than 5 μm while, simultaneously, preventing such large dose to be released in a very short period of time. Such sudden release may lead to the “powdery mouth” effect, throat irritation and large drug losses in the upper airways. The means for powerful aerosolisation and controlled powder deagglomeration and release is thus required by design.
Furthermore, the great majority of the patients requiring antibiotics, vaccines, proteins, peptides or other drugs in such applications are inhaler-naive and may not have any training in inhalation. It is thus required that the device be of extreme simplicity and intuitive to use. In addition, the developer of a disposable inhaler for high dosage drug delivery is also faced with the challenge of gaining competitive advantage through a reduction in the cost of the device, both through the use of the fewest number of components as possible and designing for fast assembly during high volume manufacturing.
2. Discussion of Prior Art
There is abundant prior art in the field of single-use disposable inhalers, but a disposable inhaler solving all the above requirements has not been provided yet. The present application is particularly directed at the inventive improvement of the inhaler described in PT103481.
Previously, as described in PT103481 and illustrated in FIG. 1a to 1c and 2a of the accompanying drawings, there was known a disposable inhaler comprising a body 101 including a mouthpiece 102 and a cartridge 103 mounted in an opening 104 provided in the body 101 and having at least one powder compartment 105. The powder compartment 105 had inlet holes 106 to admit air and outlet holes 107 to communicate with an inhalation channel 108 provided in the body 101. Furthermore, the cartridge 103 was made slidable relative to the body 101 by the patient, between a first position detailed in FIG. 1a where the compartment rear holes 106 were isolated and sealed, and a second position detailed in FIGS. 1b and 1c in which the compartment rear 106 and front 107 holes were aligned with the body inhalation channel 108, thus allowing the flow of air to disperse and entrain the powder through the mouthpiece and into the patient's mouth or nasal cavity and finally into the desired site of action. The construction disclosed in PT103481 allowed for a device with pre-filled unit doses of powder for patient convenience, disposable for reasons of safety and hygiene, simple for economic reasons and intuitive for ease of use by the patient. While this inhaler is being successfully marketed, tests indicate the maximum deliverable dose is in the region of 10-20 mg of powder.
Other single-use disposable inhalers are also already known in the prior art.
U.S. Pat. No. 5,797,392 discloses one of the simplest designs of a single-use disposable inhaler similar to a drinking straw. Although simple, the construction disclosed does not provide dispersion and deagglomeration mechanisms or features allowing the break-up of large quantities of highly cohesive drug particles and excipients down to the inhalable size while minimizing powder retention in the device.
U.S. Pat. Nos. 5,042,472, 5,239,991, 6,098,619 and WO pat. 2014/175815 disclose also other simple single-use and disposable devices apparently absent of major powder deagglomeration features and the constructions disclosed in the drawings are likely to cause the sudden release of powder leading to the undesirable “powdery mouth” and throat irritation effects.
U.S. Pat. Nos. 6,286,507, 2008/0190424 and US pat. 2009/0250058 disclose other single-use disposable inhaler constructions generally comprising a first body member including a powder compartment and a second body member which are closely fit to form an inhaler body with an outlet, where the two body member are separated by a strip or tape which exposes the powder compartment to air when pulled away from the inhaler body. However, the constructions presented rely on simple throughflows that are absent of flow patterns into the powder compartment thus preventing the application of powerful dispersion and deagglomeration forces on powders for its effective detachment from the compartment's walls, which is particularly important for the successful delivery of large payloads of cohesive powders.
U.S. Pat. No. 6,941,947 discloses another single-use dry powder inhaler having a dispersion chamber, a blister supported and adjacent to the dispersion chamber, a mouthpiece and a hinged cover. The opening movement of the hinged cover causes the blister to open and an airflow path is formed that extends under the blister and into the dispersion chamber. However, the drawings disclosed in this patent show also an apparent absence of powerful flow patterns for dispersion and deagglomeration of large payloads of powder, a construction comprising at least 4 unique components and a non-trivial assembly sequence, both adding to total manufacturing cost.
There is therefore the need for a single-use disposable device which achieves the functionalities of the disposable inhalers described above with effective aerosolisation and deagglomeration mechanisms for large payloads of very cohesive powers, in the range of 50 to 120 mg, that minimizes powder retention, that is simple and intuitive to use and that can be manufactured at a very low cost.